Striatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. Local field potential recordings in rodent striatum show dopamine-and reward-dependent transitions between two states: a "spontaneous" state involving β (*15-30 Hz) and low γ (*40-60 Hz), and a state involving θ (*4-8 Hz) and high γ (*60-100 Hz) in response to dopaminergic agonism and reward. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of these rhythms, as well as their modulation by dopamine. Building on previous modeling and experimental work suggesting that striatal projection neurons (SPNs) are capable of generating β oscillations, we show that networks of striatal fast-spiking interneurons (FSIs) are capable of generating δ/θ (ie, 2 to 6 Hz) and γ rhythms. Under simulated low dopaminergic tone our model FSI network produces low γ band oscillations, while under high dopaminergic tone the FSI network produces high γ band activity nested within a δ/θ oscillation. SPN networks produce β rhythms in both conditions, but under high dopaminergic tone, this β oscillation is interrupted by δ/θ-periodic bursts of γ-frequency FSI inhibition. Thus, in the high dopamine state, packets of FSI γ and SPN β alternate at a δ/θ timescale. In addition to a mechanistic explanation for previously observed rhythmic interactions and transitions, our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts motor function. We hypothesize that high dopamine-induced periodic FSI γ-rhythmic inhibition enables switching between β-rhythmic SPN cell assemblies representing the currently active motor program, and thus that dopamine facilitates movement in part by allowing for rapid, periodic shifts in motor program execution.

Sensorimotor adaptation-enduring changes to motor commands due to sensory feedback-allows speakers to match their articulations to intended speech acoustics. How the brain integrates auditory feedback to modify speech motor commands and what limits the degree of these modifications remain unknown. Here, we investigated the role of speech motor cortex in modifying stored speech motor plans. In a within-subjects design, participants underwent separate sessions of sham and anodal transcranial direct current stimulation (tDCS) over speech motor cortex while speaking and receiving altered auditory feedback of the first formant. Anodal tDCS increased the rate of sensorimotor adaptation for feedback perturbation. Computational modeling of our results using the Directions Into Velocities of Articulators (DIVA) framework of speech production suggested that tDCS primarily affected behavior by increasing the feedforward learning rate. This study demonstrates how focal noninvasive neurostimulation can enhance the integration of auditory feedback into speech motor plans.

Striatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. Local field potential recordings in rodent striatum show dopamine-and reward-dependent transitions between two states: a "spontaneous" state involving β (∼15-30 Hz) and low γ (∼40-60 Hz), and a state involving θ (∼4-8 Hz) and high γ (∼60-100 Hz) in response to dopaminergic agonism and reward. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of these rhythms, as well as their modulation by dopamine. Building on previous modeling and experimental work suggesting that striatal projection neurons (SPNs) are capable of generating β oscillations, we show that networks of striatal fast-spiking interneurons (FSIs) are capable of generating δ/θ (ie, 2 to 6 Hz) and γ rhythms. Under simulated low dopaminergic tone our model FSI network produces low March 8, 2020 1/50 γ band oscillations, while under high dopaminergic tone the FSI network produces high γ band activity nested within a δ/θ oscillation. SPN networks produce β rhythms in both conditions, but under high dopaminergic tone, this β oscillation is interrupted by δ/θ-periodic bursts of γ-frequency FSI inhibition. Thus, in the high dopamine state, packets of FSI γ and SPN β alternate at a δ/θ timescale. In addition to a mechanistic explanation for previously observed rhythmic interactions and transitions, our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts motor function. We hypothesize that high dopamine-induced periodic FSI γ-rhythmic inhibition enables switching between β-rhythmic SPN cell assemblies representing the currently active motor program, and thus that dopamine facilitates movement in part by allowing for rapid, periodic shifts in motor program execution. Author summaryStriatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of striatal rhythms, as well as their modulation by dopamine. Our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts the function of the motor system, enabling rapid, periodic shifts in motor program execution.As the largest structure of the basal ganglia network, the striatum is essential to motor 2 function and decision making. It is the primary target of dopaminergic (DAergic) 3 neurons in the brain, and its activity is strongly modulated by DAergic tone. Disorders 4 of the DA and motor systems, such as Parkinson's, Huntington's, Tourette's, and many ...

Rett syndrome (RTT) has a complex developmental course over childhood and adolescence. Patients with RTT often have a pre-symptomatic period with no or little outward signs of the disorder, followed by developmental arrest and regression. Following regression, the individual's condition is not static, as they often progress into defined stages with unique neurological symptoms. Similarly, the progression of RTT-like symptoms in female mice heterozygous for a null-mutation has a prodromal and symptomatic period. Change in functional local circuit connectivity was studied using hippocampal slices, assaying Schaffer evoked activity in area CA1 using fast voltage sensitive dye imaging. With this technique the local functional interactions between the excitatory and inhibitory components of the circuit can be characterized. The prodromal period was associated with a shift in extent of excitation into the stratum oriens of the hippocampus and reduced sensitivity to changes in divalent cation concentration. These data suggest that hyperexcitability of the hippocampus at the circuit level may contribute to the prodromal reduction in cognitive performance and the onset of developmental regression.

Octopamine is known to have an appetitive role in odor conditioning paradigms in Drosophila melanogaster. We wanted to test whether octopamine could also act as an appetitive stimulus in courtship conditioning, a paradigm in which training with an unreceptive female (such as a decapitated virgin) causes a subsequent decrease in courtship behavior in male Drosophila. To control octopamine release, we used the Tdc2-Gal4 and UAS-dTRPa1 genes in conjunction to depolarize octopaminergic neurons at 27 C in experimental flies. We hypothesized that inducing octopamine release during courtship training would decrease the aversive impact of training and cause less subsequent suppression of courtship behavior. Our findings confirmed this hypothesis: Tdc2-Gal4/UAS-dTRPa1 flies trained at 27 degrees showed significantly more courtship behavior than controls during testing, and in fact showed no significant effect of courtship training. This confirms that octopamine release counteracts the aversive stimulus of failure to copulate, indicating that octopamine may have an appetitive role in courtship.